Dental caries (or decay) and dental erosion are still widespread conditions, despite the fluoridation of the water supply in many countries and the use of fluoride toothpastes. Dental caries usually begins in the enamel of the tooth surface but may progressively destroy the hard tissues of the teeth. In many countries, about half of 5 year old children experience some tooth decay. In addition, some groups of people are, by virtue of their occupation, particularly susceptible to dental erosion and/or caries. For example, wine tasters and athletes such as elite cyclists who frequently sip on sports drinks, continually expose their teeth to low pH beverages which may cause the whole surface of the tooth to dissolve.
It is well known that dairy products have a protective effect against the development of dental caries. A number of investigations have suggested that it is primarily the protein component of dairy products, and casein in particular, that exerts an anticariogenic/remineralising action on tooth enamel. In addition, a particular fraction of active peptides in casein have been identified as being largely responsible for the anticariogenic/remineralising action. These are the calcium phosphate sequestering phosphopeptides, which constitute about 10% of the total weight of casein. These peptides contain a cluster of phosphoseryl residues [-Ser(P)-Ser(P)-Ser(P)-Glu-Glu] that markedly increase the solubility of calcium phosphate by forming colloidal casein phosphopeptide amorphous calcium phosphate complexes.
There are numerous patent publications directed to various compositions containing casein, caseinates, digests thereof or specific casein-derived phosphopeptides for use in caries inhibition and related dental applications.
For example, NZ patent specification 199891 describes toothpastes and dentifrices containing a caries and gingivitis inhibiting amount of casein, alpha-s-casein or phosvitin.
JP 59152317 describes an oral composition comprising mutanase (a drug for preventing tooth decay) together with casein, casein hydrolysate or a mixture thereof.
U.S. Pat. No. 5,833,953, JP 9002928 and U.S. Pat. No. 5,427,769 all describe various compositions for treating or preventing dental caries and containing micellar casein.
U.S. Pat. No. 5,130,123 describes a dentifrice composition for inhibiting caries or gingivitis containing a water soluble salt of either a caseinate or a digest of a caseinate.
WO 82/03008 describes compositions for inhibiting caries and gingivitis, containing phosphoproteins or phosphopolypeptides containing a specified amino acid sequence, and in particular sodium caseinate, calcium caseinate or phosvitin.
JP 4077415 describes a dental calculus-preventing composition containing casein phosphopeptides in combination with a suitable excipient.
U.S. Pat. No. 5,015,628 describes anticariogenic phosphopeptides having 5 to 30 amino acids and containing a specified amino acid sequence, and which may be obtained by tryptic digestion of casein.
WO 98/40406 describes specific calcium phosphopeptide complexes having anticaries efficacy. The phosphopeptides contain the Ser(p) cluster sequence motif [-Ser(P)-Ser(P)-Ser(P)-Glu-Glu], where Ser(P) is phosphoserine, and are said to be able to stabilize their own weight in amorphous calcium phosphate and amorphous calcium fluoride phosphate.
WO 00/06108 describes various formulations for the delivery of bioactive constituents to biological surfaces such as dental surfaces, comprising suspensions or solutions of one or more isolated and purified casein protein or salt thereof.
Compositions containing casein phosphopeptides have been reported as having superior anticaries/remineralising activity compared to compositions containing intact casein. However, the use of casein phosphopeptides has the disadvantage that digestion of casein (for example using the enzyme trypsin) to release the desired phosphopeptides also releases hydrophobic peptides which give the resulting digest a bitter flavour. This means that, for the product to have an acceptable flavour, fractionation of the digest to remove such hydrophobic peptides is required. In turn, this means that only a fraction of the casein-derived material is used; typically over 75% of the material is wasted.
The applicants have now surprisingly found that by partially hydrolyzing casein and subsequently partially cross-linking the partial hydrolysate, phosphoprotein preparations having superior calcium-binding and teeth remineralisation properties to those of unmodified casein or a partial casein hydrolysate can be obtained. Such phosphoprotein preparations have also been found to have an enhanced ability to bind other bioactive active metal ions.
JP 4-126039 describes a method of preparing a functional peptide by partially hydrolyzing a food protein, such as a protein obtained from soy beans, wheat or sweetcorn, or animal proteins such as gelatin, animal meat, fish meat or casein, followed by treatment of the resultant hydrolyzed peptide with transglutaminase or diluted acid. The resulting treated peptide is said to be free of bitterness. JP 4-126039 does not however describe the cation binding properties of such peptides, nor is a peptide obtained from casein specifically described therein.
WO 00/05972 and WO 01/0154512 describe chewing gum compositions containing casein or a modified casein such as polymerized hydrolyzed casein, as part of the elastomeric component of the gum. These publications do not however describe the cation binding properties of such modified casein.
It is an object of the present invention to provide methods and/or compositions useful for delivering bioactive metal ions, and methods and/or compositions for remineralising teeth, and/or preventing or treating dental caries, tooth erosion, dentinal hypersensitivity or gingivitis, which will go some way towards overcoming the disadvantages of the prior art, or at least provide the public with a useful choice.